A neo-epitope of serum lysyl oxidase like 2 (LOXL2) generated during enzyme maturation is elevated in cancer and idiopathic pulmonary disease

Background: Lysyl oxidase like 2 (LOXL2) activity is elevated in idiopathic pulmonary fibrosis (IPF) and cancer affecting collagen stability, desmoplastic- and scar tissue stiffness associated with poor prognosis. An ELISA targeting the LOXL2 neo-epitope generated through release of the signal peptide during LOXL2 maturation was developed and evaluated in patients with various cancers or IPF. Methods: The N-terminal site of the human LOXL2 was selected as target for ELISA development. A range of technical optimizations and validation steps were performed. Serum LOXL2 was measured in cohort 1: healthy controls (n=16) and in patients with stage 1-3 cancer of the breast (n=20), colon (n=7) lung (n=26), ovary (n=9), pancreas (n=5), prostate (n=14) and malignant melanoma (n=7); as well as in cohort 2: IPF (n=120) and healthy controls (n=51) Results: A technically robust and specific assay was developed showing a lower limit of detection of 5.7 ng/ml and intra- and inter-assay variations of 8% and 12%, respectively. LOXL2 was detectable in serum from healthy controls and showed reactivity towards recombinant LOXL2. Compared to controls, LOXL2 was significantly (p Conclusion: A technically robust assay specific towards a neo-epitope in LOXL2 was developed and shown to be elevated in patients with various cancer types and IPF compared to controls.